Background: Tenofovir DF (TDF) has potent in vivo and in vitro activity against both wild-type and lamivudine(LAM)-resistant hepatitis B virus (HBV). Study 903 is an ongoing, randomized, double-blind, active-controlled 144-wk trial of TDF 300 mg qd vs stavudine 40 mg bid in combination with efavirenz 600 mg qd and LAM 150 mg bid in 600 HIV treatment-naive adults. Stavudine and efavirenz have no reported anti-HBV activity.

Methods: Eleven (11) HIV/HBV co-infected patients (pts) from Study 903 (5 TDF + LAM and 6 LAM) with baseline serum HBV DNA ≥ 6 log₁₀ copies/mL and with wk 48 data, were included in this analysis (as treated). Baseline mean characteristics: age 38 yrs; plasma HIV RNA 4.8 log₁₀ copies/mL; CD4 count 204 cells/mm³; serum HBV DNA 8.6 log₁₀ copies/mL; serum ALT 86 IU/L (2.0 x ULN). There were no significant differences in baseline characteristics (p > 0.05). Ten (10) pts were HbeAg⁺ and male. Serum HBV from pts with detectable (> 1000 copies/mL) HBV DNA at wk 48 were genotypically analyzed for the development of LAM-resistance mutations (LAM^R). The 4 pts who developed the LAM^R showed a mean increase in HBV DNA of 2.3 log₁₀ from their response nadir.

 

Results:

At week 48	TDF + LAM n = 5	LAM n = 6
Mean change HBV DNA (log10 copies/mL)	-4.70	-2.95
HBV DNA < 1000 copies/mL	4	1
LAMR (YMDD mutant)	0/1	4/5
HBeAg seroconversion	1	1
Mean change ALT level (IU/L)	-55	-22
ALT > 5x ULN (weeks 0–48)	2	4

p > 0.05, for all comparisons

 

Conclusions: The combination of TDF + LAM appears to more effectively suppress both HBV replication and LAM^R development compared to LAM alone. Further study will be needed to clarify the role of TDF + LAM combination anti-HBV therapy in HIV/HBV co-infected pts.